Methimazole increases H2O2 toxicity in human thyroid epithelial cells

Hydrogen peroxide (H₂O₂) is necessary for thyroid hormone production and also for intracellular signalling purposes. Owing to its oxidative properties, however, it is harmful to cells, and deregulation of thyroid oxidative state has been implicated in the pathology of thyroid cancer. In this project, we studied the effects of H₂O₂ on morphology and histochemical indicators of differentiated function (intracellular thyroglobulin), ability to generate NADPH (glucose-6-phosphate dehydrogenase (G6PD) activity) and vitality (apoptosis assay) in human thyroid epithelial cells. We further evaluated whether methimazole, an antithyroid drug reported to have antioxidative properties, could counteract the effects of H₂O₂. Our data demonstrate tolerance to H₂O₂ in concentrations less than 0.3 mM and harmful effects at higher concentrations. 10 mM methimazole sensitizes the cells towards H₂O₂, possibly due to a dose-dependent inhibition of G6PD. Our data demonstrate the importance of this antioxidative system and point towards a relevant, but seldom recognized, influence of methimazole.